Tumor invasion and metastasis in Drosophila: A bold past, a bright future

Stefanatos, Rhoda; Vidal, Marcos

doi:10.1016/j.jgg.2011.09.004

Cited by 26 publications

(23 citation statements)

References 61 publications

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“…During the past 15 years, tumor growth in flies has been induced experimentally often in a mosaic fashion for example in the mitotically active imaginal discs, which are precursors of adult organs. Tumors were most often induced with a combination of a dominant-active form of the oncogene Ras and reduced expression of genes that define cell polarity (Brumby and Richardson, 2003; Pagliarini and Xu, 2003; Kounatidis and Ligoxygakis, 2012; Stefanatos and Vidal, 2012). Induction of mutant clones for example in the eye imaginal disc and simultaneous expression of a GFP-marker allowed measuring the tumor size in different genetic backgrounds (Uhlirova and Bohmann, 2006).…”

Section: Similarities Between Wounds and Tumors: Messages From The Flymentioning

confidence: 99%

Damage signals in the insect immune response

2014

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Insects and mammals share an ancient innate immune system comprising both humoral and cellular responses. The insect immune system consists of the fat body, which secretes effector molecules into the hemolymph and several classes of hemocytes, which reside in the hemolymph and of protective border epithelia. Key features of wound- and immune responses are shared between insect and mammalian immune systems including the mode of activation by commonly shared microbial (non-self) patterns and the recognition of these patterns by dedicated receptors. It is unclear how metazoan parasites in insects, which lack these shared motifs, are recognized. Research in recent years has demonstrated that during entry into the insect host, many eukaryotic pathogens leave traces that alert potential hosts of the damage they have aﬄicted. In accordance with terminology used in the mammalian immune systems, these signals have been dubbed danger- or damage-associated signals. Damage signals are necessary byproducts generated during entering hosts either by mechanical or proteolytic damage. Here, we briefly review the current stage of knowledge on how wound closure and wound healing during mechanical damage is regulated and how damage-related signals contribute to these processes. We also discuss how sensors of proteolytic activity induce insect innate immune responses. Strikingly damage-associated signals are also released from cells that have aberrant growth, including tumor cells. These signals may induce apoptosis in the damaged cells, the recruitment of immune cells to the aberrant tissue and even activate humoral responses. Thus, this ensures the removal of aberrant cells and compensatory proliferation to replace lost tissue. Several of these pathways may have been co-opted from wound healing and developmental processes.

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Section: Similarities Between Wounds and Tumors: Messages From The Flymentioning

confidence: 99%

Damage signals in the insect immune response

2014

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“…D. melanogaster is an excellent system in which to study tumor suppressor gene function, as many of the hallmarks of human cancer, including self-sufficiency in growth and proliferative signals, insensitivity to anti-proliferative signals, evasion of apoptosis, and invasion/metastasis can be found in this animal model for cancer [13, 33, 34]. One advantage of this system is that it permits use of FLP/FRT recombination [35] to create clones of genetically distinct somatic cells that model human tumors.…”

Section: Analysis Of D Melanogaster Fra/dcc Provides the First Direcmentioning

confidence: 99%

Deleted in Colorectal Cancer (DCC) Pathfinding: Axon Guidance Gene Finally Turned Tumor Suppressor

Duman-Scheel

2012

CDT

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Loss of heterozygosity (LOH) at human chromosome 18q, which includes the gene Deleted in Colorectal Cancer (DCC), has been linked to colorectal and many other human cancers. DCC encodes the receptor for the axon guidance molecule Netrin (Net) and functions during neural development in a variety of organisms. However, since its discovery in the 1990s, the status of DCC as a tumor suppressor has been debated, primarily due to a lack of support for this hypothesis in animal models. A recent study from our laboratory capitalized on the genetic tractability of Drosophila melanogaster to demonstrate that this gene functions as an invasive tumor suppressor, thereby providing the first direct link between DCC loss and metastatic phenotypes in an animal model for cancer. Two subsequent studies from other laboratories have demonstrated that DCC suppresses tumor progression and metastasis in murine colorectal and mammary tumor models. Combined, these findings have prompted the rebirth of DCC as a tumor suppressor and highlighted the need for continued analysis of DCC function in animal models for human cancer.

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“…Tumor invasion and metastasis are complicated processes, involving the activities of tumor cells and host cells, which are regulated by multiple tumor-related genes (6,7). One of the most significant steps in the invasion and metastasis cascade involves the destruction of the extracellular matrix (ECM) and basement membranes, allowing tumor cells to invade into and grow at sites distant from the original tumor site (8)(9)(10).…”

Section: Introductionmentioning

confidence: 99%

Celastrol negatively regulates cell invasion and migration ability of human osteosarcoma via downregulation of the PI3K/Akt/NF-κB signaling pathway in vitro

Wang

Zhou

et al. 2016

Oncology Letters

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Abstract. Osteosarcoma (OS) is a primary malignant tumor of the bone, with a tendency to metastasize early. Despite the advances in treatment options, more than 30% of patients develop distant metastases, and the prognosis of these patients with metastases is extremely poor. Celastrol has been demonstrated to manifest multiple pharmacological activities, including induction of apoptosis in numerous types of cancer cell lines. Our previous studies have also suggested that Celastrol is capable of inducing apoptosis of human osteosarcoma cells via the mitochondrial-dependent pathway. The purpose of this study was to investigate the effects of Celastrol on the migration and invasion of human osteosarcoma U-2OS cells in vitro. Cell migration and invasion were investigated using wound healing and Boyden chamber Transwell assays. We observed that Celastrol suppressed cell invasion and migration in human osteosarcoma U-2OS cells. Furthermore, protein expression levels of phosphorylated phosphatidylinositol 3-kinase (PI3K), Akt, inhibitor of κB kinase α/β, inhibitor of κB α, nuclear factor-κB (NF-κB subunit p65) and matrix metallo proteinase (MMP)-2 and -9 were measured by western blot analysis. We observed that the PI3K/Akt/NF-κB signaling pathway was inhibited following Celastrol treatment. In addition, the expression levels of MMP-2 and -9 proteins were also reduced significantly following Celastrol treatment. Therefore, we confirmed that Celastrol suppressed osteosarcoma U-2OS cell metastasis via downregulation of the PI3K/Akt/NF-κB signaling pathway in vitro.

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Tumor invasion and metastasis in Drosophila: A bold past, a bright future

Cited by 26 publications

References 61 publications

Damage signals in the insect immune response

Damage signals in the insect immune response

Deleted in Colorectal Cancer (DCC) Pathfinding: Axon Guidance Gene Finally Turned Tumor Suppressor

Celastrol negatively regulates cell invasion and migration ability of human osteosarcoma via downregulation of the PI3K/Akt/NF-κB signaling pathway in vitro

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